tbuckley/cabot-search huggingface dataset:
Osteoblastoma of the Lumbar Spine
Authors: Alfredo Laverde Mächler, Juan Pablo Suárez Fernández, María Luz Domínguez Grande, Carmen Vigil Díaz, Francisco Manuel González García
Journal: Clinical Nuclear Medicine (2021)

Osteoblastoma is an uncommon benign osteoid tissue-forming bone tumor. We present the case of a 16-year-old adolescent boy with lower back pain that radiated down the right thigh. Lumbar MRI and CT findings were consistent with a long-standing osteoid osteoma located in the right laminae and pedicle of L3. SPECT/CT with 99mTc-DPD showed a highly increased osteogenic activity within the lesion, especially in the core region, also suggesting an osteoid osteoma. Surgical en bloc resection was performed with a final histological diagnosis of osteoblastoma.
COVID Lessons Continue
Authors: Hina J. Shah, Jason I. Halpern, Gaurav V. Watane, Hyewon Hyun
Journal: Clinical Nuclear Medicine (2021)

COVID vaccination has begun in most of the countries. Older population and high-risk groups are prioritized for vaccination. Postvaccination imaging in cancer patients may show effects of the immune response to the vaccine. As such, it is important to know the timing and laterality of the vaccination as the reactive lymph nodes in the ipsilateral axilla can be seen on the imaging. We present a case of DOTATATE-avid nonpathologically enlarged lymph nodes in ipsilateral axilla and linear tracer uptake in the deltoid muscle on a patient imaged for a recent diagnosis of rectal neuroendocrine neoplasm.
Re: Quality and Safety in Healthcare, Part LXVIII: Consequences and More Solutions Regarding Poor Well-Being in Medical Students
Authors: Vanessa Murad, Patricia Bernal, Camilo Barragán
Journal: Clinical Nuclear Medicine (2021)

∗Department of Nuclear Medicine Seoul National University Hospital Seoul, South Korea [email protected] †Department of Radiology and Diagnostic Imaging at Fundacion Santa Fe of Bogota University Hospital, Bogota, Colombia Conflicts of interest and sources of funding: none declared. This article does not contain any studies with animals or human participants performed by any of the authors.
Orbital Plasmablastic Lymphoma
Authors: Himanshu Bansal, Mudalsha Ravina, Pradeep Kumar Chandrakar, Tinu Thadiyananickal Lukose, Sarin Krishna
Journal: Clinical Nuclear Medicine (2021)

Abstract Plasmablastic lymphoma (PBL) is a rare and aggressive variant of diffuse large B-cell lymphoma which is associated with HIV infection. Recently, it has also been reported in immunocompetent and solid organ transplant patients. PBL commonly presents in extranodal regions such as oral cavity, digestive tract, and skin. Orbital involvement by PBL is extremely rare with only few reports in the literature. We present a case of PBL involving the bilateral orbits in an immunocompetent patient with 1-year follow-up on 18 F-FDG PET/CT scan.
Quality and Safety in Healthcare, Part LXXIV
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2020)

Abstract Disruptive behavior has major adverse consequences for patient care, morale of the staff, and institutional reputation. Disruptive actions must be confronted as soon as is feasible. Usually, such behavior will not recur following 1 more firm conversations by officials of the healthcare institution, but if necessary disciplinary measures and/or remediation may be necessary. Rarely, because of egregious or repeated offenses, it may be obligatory to suspend the privileges of the individual permanently or until there is further evaluation, such as by a subcommittee of the medical executive committee or perhaps by a fitness-for-duty assessment by an outside organization.
Löfgren Syndrome on 18F-FDG PET/CT
Authors: Suzanne J. M. Tol, Friso M. van der Zant, Remco J. J. Knol, Maurits Wondergem, Wouter A. M. Broos
Journal: Clinical Nuclear Medicine (2021)

Abstract A 58-year-old man presented with fever, erythema nodosum, and arthralgia of knee and ankle joints. Laboratory data showed signs of inflammation, and chest x-ray revealed bilateral hilar lymphadenopathy. 18 F-FDG PET/CT was acquired to analyze the underlying causes and revealed FDG accumulation in thoracic lymphadenopathy and in subcutaneous lesions and periarticular uptake. This typical triad is known as Löfgren syndrome, an acute manifestation of sarcoidosis and which, as this case shows, can be visualized on 18 F-FDG PET/CT. It is important to recognize this syndrome and to discriminate it from the classic presentation of sarcoidosis because of its different diagnostic and therapeutic consequences.
Malignant Melanoma of Glans Penis
Authors: Hemant Sachani, Sarthak Tripathy, Shamim Ahmed Shamim, Sameer Rastogi, Annie K. Baa
Journal: Clinical Nuclear Medicine (2021)

Melanomas usually arise in the sun exposed parts of the skin. Mucosal melanoma is a rare condition. Melanoma of glans penis is even a rarer phenomenon with less than 250 cases reported in literature so far. Here we present a case of a 55-year-old man diagnosed with melanoma of glans penis with findings on 18F FDG PET/CT scan done for metastatic workup. 18F-FDG PET/CT showed primary in the glans penis with metastases in the right supraclavicular, mediastinal, and abdominal lymph nodes.
A Rare Cause of SCC Antigen Elevation
Authors: Virginie Huchet, Vincent Cockenpot, Maria Lesnik, Marie Luporsi, Nina Jehanno
Journal: Clinical Nuclear Medicine (2021)

We report the case of a 68-year-old woman who underwent 18F-FDG PET/CT for squamous cell carcinoma antigen (SCC Ag) elevation in the follow-up of a uterine cervical cancer. The examination showed an FDG-avid mass of the left nasal cavity with left maxillary sinusitis and no other site of abnormal FDG uptake. Surgical resection of the nasal polyp was performed, and pathological examination of the specimen revealed an inverted sinonasal papilloma. SCC Ag returned to normal after surgery. Inverted sinonasal papilloma is a rare cause of SCC Ag elevation, which can be depicted by 18F-FDG PET/CT.
Cavernous Hemangioma
Authors: Valentina Scolozzi, Romina Grazia Giancipoli, Maria Cristina Macciomei, Leonardo Vigna, Lucia Leccisotti
Journal: Clinical Nuclear Medicine (2021)

We report the case of a 72-year-old woman who underwent neoadjuvant chemotherapy, right quadrantectomy (invasive ductal carcinoma, G3, pT2pN1pMx), and adjuvant radiotherapy. Two years later, a follow-up CT revealed a hepatic nodule of approximately 1 cm suspected for metastasis. 18F-FDG PET/CT was performed for restaging. Standard total-body 18F-FDG PET/CT acquisition showed no abnormal 18F-FDG uptake in the hepatic nodule. A delayed 18F-FDG PET/CT acquisition of upper abdomen was performed at 180 minutes postradiopharmaceutical injection and showed increased 18F-FDG uptake in the hepatic nodule. After nodule resection, the histological examination proved a cavernous hemangioma.
TRAF4 Maintains Deubiquitination of Caveolin-1 to Drive Glioblastoma Stemness and Temozolomide Resistance
Authors: Yongxu Li, Tiepeng Wang, Quan Wan, Qing Wang, Zhenzhong Chen, Yuan Gao, Yuchen Ye, Jiusheng Lin, Bihuan Zhao, Huaile Wang, Jinming Yang, Kai Zhao, Na Lu
Journal: Cancer Research (2022)

Abstract Glioblastoma (GBM) is the most common type of primary adult brain tumor. Glioma stem cell (GSC) residence and temozolomide (TMZ) resistance in GBM both contribute to poor patient outcome. TRAF4 is a scaffold protein with E3 ubiquitin ligase activity that has recently been discovered to promote invasion and metastasis in several malignancies, but the effects and functions of TRAF4 in GBM remain to be determined. Here, we report that TRAF4 is preferentially overexpressed in GSCs and is required for stem-like properties as well as TMZ sensitivity in GBM cells. TRAF4 specifically interacted with the N-terminal tail of Caveolin-1 (CAV1), an important contributor to the tumorigenicity of GBM cells. TRAF4 regulated CAV1 stability by preventing ZNRF1-mediated ubiquitination and facilitating USP7-mediated deubiquitination independently of its E3 ubiquitin ligase catalytic activity. TRAF4-mediated stabilization of CAV1 activated protumorigenic AKT/ERK1/2 signaling, and disruption of this axis resulted in defects in stemness maintenance. In addition, expression of TRAF4 and CAV1 was positively correlated and predicted poor prognosis in human GBM samples. Screening of common nervous system drugs identified risperidone interaction with TRAF4, and risperidone treatment resulted in the dissociation of TRAF4 and CAV1. Importantly, pharmacologic inhibition of TRAF4 with risperidone potently inhibited self-renewal, abrogated tumorigenicity, and reversed TMZ resistance in GBM. Overall, TRAF4-mediated stabilization of CAV1 promotes stemness and TMZ resistance in GBM, providing a therapeutic strategy that could improve patient outcomes. Significance: The identification of a TRAF4/Caveolin-1 axis that plays a crucial role in malignant progression of glioblastoma provides new insights into the function of TRAF4 in ubiquitin signaling and suggests TRAF4 as a potential therapeutic target.
GLS2 Is a Tumor Suppressor and a Regulator of Ferroptosis in Hepatocellular Carcinoma
Authors: Sawako Suzuki, Divya Venkatesh, Hiroaki Kanda, Akitoshi Nakayama, Hiroyuki Hosokawa, Eunyoung Lee, Takashi Miki, Brent R. Stockwell, Koutaro Yokote, Tomoaki Tanaka, Carol Prives
Journal: Cancer Research (2022)

Abstract Glutamine synthase 2 (GLS2) is a key regulator of glutaminolysis and has been previously implicated in activities consistent with tumor suppression. Here we generated Gls2 knockout (KO) mice that develop late-occurring B-cell lymphomas and hepatocellular carcinomas (HCC). Further, Gls2 KO mice subjected to the hepatocarcinogenic Stelic Animal Model (STAM) protocol produce larger HCC tumors than seen in wild-type (WT) mice. GLS2 has been shown to promote ferroptosis, a form of cell death characterized by iron-dependent accumulation of lipid peroxides. In line with this, GLS2 deficiency, either in cells derived from Gls2 KO mice or in human cancer cells depleted of GLS2, conferred significant resistance to ferroptosis. Mechanistically, GLS2, but not GLS1, increased lipid reactive oxygen species (ROS) production by facilitating the conversion of glutamate to α-ketoglutarate (αKG), thereby promoting ferroptosis. Ectopic expression of WT GLS2 in a human hepatic adenocarcinoma xenograft model significantly reduced tumor size; this effect was nullified by either expressing a catalytically inactive form of GLS2 or by blocking ferroptosis. Furthermore, analysis of cancer patient datasets supported a role for GLS2-mediated regulation of ferroptosis in human tumor suppression. These data suggest that GLS2 is a bona fide tumor suppressor and that its ability to favor ferroptosis by regulating glutaminolysis contributes to its tumor suppressive function. Significance: This study demonstrates that the key regulator of glutaminolysis, GLS2, can limit HCC in vivo by promoting ferroptosis through αKG-dependent lipid ROS, which in turn might lay the foundation for a novel therapeutic approach.
A Cancer Cell–Intrinsic GOT2–PPARδ Axis Suppresses Antitumor Immunity
Authors: Jaime Abrego, Hannah Sanford-Crane, Chet Oon, Xu Xiao, Courtney B. Betts, Duanchen Sun, Shanthi Nagarajan, Luis Diaz, Holly Sandborg, Sohinee Bhattacharyya, Zheng Xia, Lisa M. Coussens, Peter Tontonoz, Mara H. Sherman
Journal: Cancer Discovery (2022)

Despite significant recent advances in precision medicine, pancreatic ductal adenocarcinoma (PDAC) remains near uniformly lethal. Although immune-modulatory therapies hold promise to meaningfully improve outcomes for patients with PDAC, the development of such therapies requires an improved understanding of the immune evasion mechanisms that characterize the PDAC microenvironment. Here, we show that cancer cell-intrinsic glutamic-oxaloacetic transaminase 2 (GOT2) shapes the immune microenvironment to suppress antitumor immunity. Mechanistically, we find that GOT2 functions beyond its established role in the malate-aspartate shuttle and promotes the transcriptional activity of nuclear receptor peroxisome proliferator-activated receptor delta (PPARδ), facilitated by direct fatty acid binding. Although GOT2 is dispensable for cancer cell proliferation in vivo, the GOT2-PPARδ axis promotes spatial restriction of both CD4+ and CD8+ T cells from the tumor microenvironment. Our results demonstrate a noncanonical function for an established mitochondrial enzyme in transcriptional regulation of immune evasion, which may be exploitable to promote a productive antitumor immune response. Prior studies demonstrate the important moonlighting functions of metabolic enzymes in cancer. We find that the mitochondrial transaminase GOT2 binds directly to fatty acid ligands that regulate the nuclear receptor PPARδ, and this functional interaction critically regulates the immune microenvironment of pancreatic cancer to promote tumor progression. See related commentary by Nwosu and di Magliano, p. 2237.. This article is highlighted in the In This Issue feature, p. 2221.
SARS-CoV-2 S2–targeted vaccination elicits broadly neutralizing antibodies
Authors: Kevin W. Ng, Nikhil Faulkner, Katja Finsterbusch, Mary Wu, Ruth Harvey, Saira Hussain, Maria Greco, Yafei Liu, Svend Kjaer, Charles Swanton, Sonia Gandhi, Rupert Beale, Steve J. Gamblin, Peter Cherepanov, John McCauley, Rodney Daniels, Michael Howell, Hisashi Arase, Andreas Wack, David L.V. Bauer, George Kassiotis
Journal: Science Translational Medicine (2022)

Several variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged during the current coronavirus disease 2019 (COVID-19) pandemic. Although antibody cross-reactivity with the spike glycoproteins (S) of diverse coronaviruses, including endemic common cold coronaviruses (HCoVs), has been documented, it remains unclear whether such antibody responses, typically targeting the conserved S2 subunit, contribute to protection when induced by infection or through vaccination. Using a mouse model, we found that prior HCoV-OC43 S–targeted immunity primes neutralizing antibody responses to otherwise subimmunogenic SARS-CoV-2 S exposure and promotes S2-targeting antibody responses. Moreover, vaccination with SARS-CoV-2 S2 elicited antibodies in mice that neutralized diverse animal and human alphacoronaviruses and betacoronaviruses in vitro and provided a degree of protection against SARS-CoV-2 challenge in vivo. Last, in mice with a history of SARS-CoV-2 Wuhan–based S vaccination, further S2 vaccination induced broader neutralizing antibody response than booster Wuhan S vaccination, suggesting that it may prevent repertoire focusing caused by repeated homologous vaccination. These data establish the protective value of an S2-targeting vaccine and support the notion that S2 vaccination may better prepare the immune system to respond to the changing nature of the S1 subunit in SARS-CoV-2 variants of concern, as well as to future coronavirus zoonoses.
Comparison of Tofogliflozin and Glimepiride Effects on Nonalcoholic Fatty Liver Disease in Participants With Type 2 Diabetes: A Randomized, 48-Week, Open-Label, Active-Controlled Trial
Authors: Yumie Takeshita, Masao Honda, Kenichi Harada, Yuki Kita, Noboru Takata, Hiromasa Tsujiguchi, Takeo Tanaka, Hisanori Goto, Yujiro Nakano, Noriho Iida, Kuniaki Arai, Tatsuya Yamashita, Eishiro Mizukoshi, Hiroyuki Nakamura, Shuichi Kaneko, Toshinari Takamura
Journal: Diabetes Care (2022)

OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is a liver phenotype of type 2 diabetes and obesity. Currently, the efficacy of sodium–glucose cotransporter 2 (SGLT2) inhibitors and sulfonylureas in liver pathology and hepatic gene expression profiles for type 2 diabetes with NAFLD are unknown. RESEARCH DESIGN AND METHODS We conducted a 48 week, randomized, open-label, parallel-group trial involving participants with biopsy-confirmed NAFLD. A total of 40 participants were randomly assigned to receive once daily 20 mg tofogliflozin or 0.5 mg glimepiride. The primary outcome was the percentage of participants with at least an improvement in all individual scores for histological categories of steatosis, hepatocellular ballooning, lobular inflammation, and fibrosis by at least 1 point. The secondary end points were the changes in liver enzymes, metabolic markers, and hepatic gene expression profiles. RESULTS Fibrosis scores improved in the tofogliflozin group (60%, P = 0.001), whereas the change from baseline did not differ significantly between the groups (P = 0.172). The histological variables of steatosis (65%, P = 0.001), hepatocellular ballooning (55%, P = 0.002), and lobular inflammation (50%, P = 0.003) were improved in the tofogliflozin group, whereas only hepatocellular ballooning was improved in the glimepiride group (25%, P = 0.025). Hepatic gene expression profiling revealed histology-associated signatures in energy metabolism, inflammation, and fibrosis that were reversed with tofogliflozin. CONCLUSIONS Tofogliflozin and, to a lesser degree, glimepiride led to liver histological and metabolic improvement in participants with type 2 diabetes and NAFLD, with no significant difference between the agents. The hepatic expression of the genes involved in energy metabolism, inflammation, and fibrosis was well correlated with liver histological changes and rescued by tofogliflozin. We need further confirmation through long-term larger-scale clinical trials of SGLT2 inhibitors.
GOT2 Silencing Promotes Reprogramming of Glutamine Metabolism and Sensitizes Hepatocellular Carcinoma to Glutaminase Inhibitors
Authors: Yunzheng Li, Binghua Li, Yanchao Xu, Liyuan Qian, Tiancheng Xu, Gang Meng, Huan Li, Ye Wang, Laizhu Zhang, Xiang Jiang, Qi Liu, Yuanyuan Xie, Chunxiao Cheng, Beicheng Sun, Decai Yu
Journal: Cancer Research (2022)

Abstract Hepatocellular carcinoma (HCC) is one of the primary liver malignancies with a poor prognosis. Glutamic-oxaloacetic transaminase 2 (GOT2) is a highly tissue-specific gene in the liver, but the roles GOT2 plays in the progression of HCC remain unclear. Here, we report that GOT2 is downregulated in HCC tumor tissues and that low expression of GOT2 is associated with advanced progression and poor prognosis. In HCC cells, knockdown of GOT2 promoted proliferation, migration, and invasion. In mouse models of HCC, loss of GOT2 promoted tumor growth as well as hematogenous and intrahepatic metastasis. Mechanistically, silencing of GOT2 enhanced glutaminolysis, nucleotide synthesis, and glutathione synthesis by reprogramming glutamine metabolism to support the cellular antioxidant system, which activated the PI3K/AKT/mTOR pathway to contribute to HCC progression. Furthermore, HCC with low expression of GOT2 was highly dependent on glutamine metabolism and sensitive to the glutaminase inhibitor CB-839 in vitro and in vivo. Overall, GOT2 is involved in glutamine metabolic reprogramming to promote HCC progression and may serve as a therapeutic and diagnostic target for HCC. Significance: Altered glutamine metabolism induced by GOT2 loss supports HCC growth and metastasis but confers a targetable vulnerability to glutaminase inhibitors.
Engineering a Hierarchical Biphasic Gel for Subcutaneous Vascularization
Authors: Daqian Gao, Alexander U. Ernst, Xi Wang, Longhai Wang, Wanjun Liu, Minglin Ma
Journal: Advanced Healthcare Materials (2022)

Implanted cell-containing grafts require a robust and functional vasculature to supply oxygen and nutrients, as well as clear metabolic waste products. However, it remains challenging to fabricate tunable, vascular-promoting scaffolds without incorporating additional biologics. Here, a biphasic gel consisting of a highly porous aerogel and a degradable fibrin hydrogel for inducing vascularization is presented. The highly porous (>90%) and stable aerogel is assembled from short microfibers by being dispersed in an aqueous solution that can be 3D printed into various configurations. The biphasic gel demonstrates good compression-resistance: 70.30% Young's modulus is recovered over 20 cycles of 65% compression under water. Furthermore, it is confirmed that tissue cells and blood vessels can penetrate a thick (≈3 mm) biphasic gel in the subcutaneous space of mice. Finally, the biphasic gel doubles the vascular ingrowth compared to a composite of a commercial surgical polyester felt and a fibrin hydrogel upon subcutaneous implantation in mice after 4 weeks. The design of this biphasic gel may advance the development of vascularized scaffolds.
Network Tau spreading is vulnerable to the expression gradients of <i>APOE</i> and glutamatergic-related genes
Authors: Victor Montal, Ibai Diez, Chan-Mi Kim, William Orwig, Elisenda Bueichekú, Raquel Gutiérrez-Zúñiga, Alexandre Bejanin, Jordi Pegueroles, Oriol Dols-Icardo, Patrizia Vannini, Georges El-Fakhri, Keith A. Johnson, Reisa A. Sperling, Juan Fortea, Jorge Sepulcre
Journal: Science Translational Medicine (2022)

A key hallmark of Alzheimer’s disease (AD) pathology is the intracellular accumulation of tau protein in the form of neurofibrillary tangles across large-scale networks of the human brain cortex. Currently, it is still unclear how tau accumulates within specific cortical systems and whether in situ genetic traits play a role in this circuit-based propagation progression. In this study, using two independent cohorts of cognitively normal older participants, we reveal the brain network foundation of tau spreading and its association with using high-resolution transcriptomic genetic data. We observed that specific connectomic and genetic gradients exist along the tau spreading network. In particular, we identified 577 genes whose expression is associated with the spatial spreading of tau. Within this set of genes, APOE and glutamatergic synaptic genes, such as SLC1A2 , play a central role. Thus, our study characterizes neurogenetic topological vulnerabilities in distinctive brain circuits of tau spreading and suggests that drug development strategies targeting the gradient expression of this set of genes should be explored to help reduce or prevent pathological tau accumulation.